6 results on '"Jay Ciezki"'
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2. PARP inhibition sensitizes to low dose-rate radiation TMPRSS2-ERG fusion gene-expressing and PTEN-deficient prostate cancer cells.
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Payel Chatterjee, Gaurav S Choudhary, Arishya Sharma, Kamini Singh, Warren D Heston, Jay Ciezki, Eric A Klein, and Alexandru Almasan
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Medicine ,Science - Abstract
Exposure to genotoxic agents, such as irradiation produces DNA damage, the toxicity of which is augmented when the DNA repair is impaired. Poly (ADP-ribose) polymerase (PARP) inhibitors were found to be "synthetic lethal" in cells deficient in BRCA1 and BRCA2 that impair homologous recombination. However, since many tumors, including prostate cancer (PCa) rarely have on such mutations, there is considerable interest in finding alternative determinants of PARP inhibitor sensitivity. We evaluated the effectiveness of radiation in combination with the PARP inhibitor, rucaparib in PCa cells. The combination index for clonogenic survival following radiation and rucaparib treatments revealed synergistic interactions in a panel of PCa cell lines, being strongest for LNCaP and VCaP cells that express ETS gene fusion proteins. These findings correlated with synergistic interactions for senescence activation, as indicated by β--galactosidase staining. Absence of PTEN and presence of ETS gene fusion thus facilitated activation of senescence, which contributed to decreased clonogenic survival. Increased radiosensitivity in the presence of rucaparib was associated with persistent DNA breaks, as determined by χ-H2AX, p53BP1, and Rad51 foci. VCaP cells, which harbor the TMPRSS2-ERG gene fusion and PC3 cells that stably express a similar construct (fusion III) showed enhanced sensitivity towards rucaparib, which, in turn, increased the radiation response to a similar extent as the DNA-PKcs inhibitor NU7441. Rucaparib radiosensitized PCa cells, with a clear benefit of low dose-rate radiation (LDR) administered over a longer period of time that caused enhanced DNA damage. LDR mimicking brachytherapy, which is used successfully in the clinic, was most effective when combined with rucaparib by inducing persistent DNA damage and senescence, leading to decreased clonogenic survival. This combination was most effective in the presence of the TMPRSS2-ERG and in the absence of PTEN, indicating clinical potential for brachytherapy in patients with intermediate and high risk PCa.
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- 2013
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3. External Beam Radiation Therapy or Brachytherapy With or Without Short Course Neoadjuvant Androgen Deprivation Therapy: Results of a Multi-Center, Prospective Study of Quality of Life
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Hiram A. Gay, Martin G. Sanda, Jingxia Liu, Ningying Wu, Daniel A. Hamstra, John T. Wei, Rodney L. Dunn, Eric A. Klein, Howard M. Sandler, Christopher S. Saigal, Mark S. Litwin, Deborah A. Kuban, Larry Hembroff, Meredith M. Regan, Peter Chang, Jeff M. Michalski, Meredith Regan, Dan Hamstra, Rodney Dunn, Laurel Northouse, David Wood, Jay Ciezki, Jeff Michalski, Gerald Andriole, Christopher Saigal, Thomas Greenfield, Louis Pisters, Deborah Kuban, Howard Sandler, Jim Hu, Adam Kibel, Douglas Dahl, Anthony Zietman, Irving Kaplan, and Andrew Wagner
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Male ,Cancer Research ,Time Factors ,medicine.medical_treatment ,Brachytherapy ,030232 urology & nephrology ,Androgen deprivation therapy ,Prostate cancer ,0302 clinical medicine ,Erectile Dysfunction ,Quality of life ,Surveys and Questionnaires ,Breast ,Prospective Studies ,Prospective cohort study ,Fatigue ,Aged, 80 and over ,Radiation ,Depression ,Penile Erection ,Middle Aged ,Combined Modality Therapy ,Neoadjuvant Therapy ,Oncology ,Radiology Nuclear Medicine and imaging ,030220 oncology & carcinogenesis ,medicine.medical_specialty ,Article ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Orgasm ,Aged ,Chi-Square Distribution ,business.industry ,Body Weight ,Prostatic Neoplasms ,Androgen Antagonists ,Prostate-Specific Antigen ,medicine.disease ,Radiation therapy ,Hot Flashes ,Quality of Life ,Physical therapy ,business ,Sexual function ,Chi-squared distribution - Abstract
Purpose The long-term effects of neoadjuvant androgen deprivation therapy (NADT) with radiation therapy on participant-reported health-related quality of life (HRQOL) have not been characterized in prospective multicenter studies. We evaluated HRQOL for 2 years among participants undergoing radiation therapy (RT) with or without NADT for newly diagnosed, early-stage prostate cancer. Methods and Materials We analyzed longitudinal cohort data from the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment Consortium to ascertain the HRQOL trajectory of men receiving NADT with external beam RT (EBRT) or brachytherapy. HRQOL was measured using the expanded prostate cancer index composite 26-item questionnaire at 2, 6, 12, and 24 months after the initiation of NADT. We used the χ 2 or Fisher exact test to compare the shift in percentages between groups that did or did not receive NADT. Analyses were conducted at the 2-sided 5% significance level. Results For subjects receiving EBRT, questions regarding the ability to have an erection, ability to reach an orgasm, quality of erections, frequency of erections, ability to function sexually, and lack of energy were in a significantly worse dichotomized category for the patients receiving NADT. Comparing the baseline versus 24-month outcomes, 24%, 23%, and 30% of participants receiving EBRT plus NADT shifted to the worse dichotomized category for the ability to reach an orgasm, quality of erections, and ability to function sexually compared with 14%, 13%, and 16% in the EBRT group, respectively. Conclusions Compared with baseline, at 2 years, participants receiving NADT plus EBRT compared with EBRT alone had worse HRQOL, as measured by the ability to reach orgasm, quality of erections, and ability to function sexually. However, no difference was found in the ability to have an erection, frequency of erections, overall sexual function, hot flashes, breast tenderness/enlargement, depression, lack of energy, or change in body weight. The improved survival in intermediate- and high-risk patients receiving NADT and EBRT necessitates pretreatment counseling of the HRQOL effect of NADT and EBRT.
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- 2017
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4. Multi-institutional Prospective Evaluation of Bowel Quality of Life After Prostate External Beam Radiation Therapy Identifies Patient and Treatment Factors Associated With Patient-Reported Outcomes: The PROSTQA Experience
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Daniel A, Hamstra, Anna S C, Conlon, Stephanie, Daignault, Rodney L, Dunn, Howard M, Sandler, A Larry, Hembroff, Anthony L, Zietman, Irving, Kaplan, Jay, Ciezki, Deborah A, Kuban, John T, Wei, Martin G, Sanda, and Jeff M, Michalski
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Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Severity of Illness Index ,Prostate cancer ,Quality of life ,Interquartile range ,Internal medicine ,Severity of illness ,Confidence Intervals ,medicine ,Humans ,Fecal incontinence ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Prospective cohort study ,Aged ,Aged, 80 and over ,Analysis of Variance ,Radiation ,Aspirin ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,Prostate ,Rectum ,Prostatic Neoplasms ,Radiotherapy Dosage ,Middle Aged ,medicine.disease ,United States ,Surgery ,Radiation therapy ,Rectal Diseases ,Oncology ,Patient Satisfaction ,Quality of Life ,Bowel urgency ,Radiotherapy, Intensity-Modulated ,medicine.symptom ,Gastrointestinal Hemorrhage ,business ,Fecal Incontinence - Abstract
Purpose To evaluate patients treated with external beam radiation therapy as part of the multicenter Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROSTQA), to identify factors associated with posttreatment patient-reported bowel health-related quality of life (HRQOL). Methods and Materials Pretreatment characteristics and treatment details among 292 men were evaluated using a general linear mixed model for their association with measured HRQOL by the Expanded Prostate Cancer Index Composite instrument through 2 years after enrollment. Results Bowel HRQOL had a median score of 100 (interquartile range 91.7-100) pretreatment and 95.8 (interquartile range 83.3-100) at 2 years, representing new moderate/big problems in 11% for urgency, 7% for frequency, 4% for bloody stools, and 8% for an overall bowel problems. Baseline bowel score was the strongest predictor for all 2-year endpoints. In multivariable models, a volume of rectum ≥25% treated to 70 Gy (V70) yielded a clinically significant 9.3-point lower bowel score (95% confidence interval [CI] 16.8-1.7, P =.015) and predicted increased risks for moderate to big fecal incontinence ( P =.0008). No other radiation therapy treatment-related variables influenced moderate to big changes in rectal HRQOL. However, on multivariate analyses V70 ≥25% was associated with increases in small, moderate, or big problems with the following: incontinence (3.9-fold; 95% CI 1.1-13.4, P =.03), rectal bleeding (3.6-fold; 95% CI 1.3-10.2, P =.018), and bowel urgency (2.9-fold; 95% CI 1.1-7.6, P =.026). Aspirin use correlated with a clinically significant 4.7-point lower bowel summary score (95% CI 9.0-0.4, P =.03) and an increase in small, moderate, or big problems with bloody stools (2.8-fold; 95% CI 1.2-6.4, P =.018). Intensity modulated radiation therapy was associated with higher radiation therapy doses to the prostate and lower doses to the rectum but did not independently correlate with bowel HRQOL. Conclusion After contemporary dose-escalated external beam radiation therapy up to 11% of patients have newly identified moderate/big problems with bowel HRQOL 2 years after treatment. Bowel HRQOL is related to baseline function, rectal V70, and aspirin use. Finally, our findings validate the commonly utilized cut-point of rectal V70 ≥25% as having significant impact on patient-reported outcomes.
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- 2013
5. Patient-reported quality of life after stereotactic body radiotherapy (SBRT), intensity modulated radiotherapy (IMRT), and brachytherapy
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Joseph R, Evans, Shuang, Zhao, Stephanie, Daignault, Martin G, Sanda, Jeff, Michalski, Howard M, Sandler, Deborah A, Kuban, Jay, Ciezki, Irving D, Kaplan, Anthony L, Zietman, Larry, Hembroff, Felix Y, Feng, Simeng, Suy, Ted A, Skolarus, Patrick W, McLaughlin, John T, Wei, Rodney L, Dunn, Steven E, Finkelstein, Constantine A, Mantz, Sean P, Collins, and Daniel A, Hamstra
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Oncology ,Male ,medicine.medical_specialty ,Multivariate analysis ,medicine.medical_treatment ,Urinary system ,Brachytherapy ,Urinary incontinence ,Radiosurgery ,Cohort Studies ,Prostate cancer ,Quality of life ,Internal medicine ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Aged ,business.industry ,Prostatic Neoplasms ,Hematology ,Middle Aged ,medicine.disease ,Radiation therapy ,Intestinal Diseases ,Sexual Dysfunction, Physiological ,Urinary Incontinence ,Quality of Life ,Radiology ,Radiotherapy, Intensity-Modulated ,Self Report ,medicine.symptom ,business - Abstract
Background and purpose Stereotactic body radiotherapy (SBRT) is being used for prostate cancer, but concerns persist about toxicity compared to other radiotherapy options. Materials and methods We conducted a multi-institutional pooled cohort analysis of patient-reported quality of life (QOL) [EPIC-26] before and after intensity-modulated radiotherapy (IMRT), brachytherapy, or SBRT for localized prostate cancer. Data were analyzed by mean domain score, minimal clinically detectable difference (MCD) in domain score, and multivariate analyses to determine factors associated with domain scores at 2-years. Results Data were analyzed from 803 patients at baseline and 645 at 2-years. Mean declines at 2-years across all patients were −1.9, −4.8, −4.9, and −13.3points for urinary obstructive, urinary incontinence, bowel, and sexual symptom domains, respectively, corresponding to MCD in 29%, 20%, and 28% of patients. On multivariate analysis (vs. IMRT), brachytherapy had worse urinary irritation at 2-years (−6.8points, p p >0.15). QOL after SBRT was similar for urinary ( p >0.5) and sexual domains ( p =0.57), but was associated with better bowel score (+6.7points, p Conclusions QOL 2-years after brachytherapy, IMRT, or SBRT is very good and largely similar, with small differences in urinary and bowel QOL that are likely minimized by modern techniques.
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- 2015
6. Minimally Important Difference for the Expanded Prostate Cancer Index Composite Short Form
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Ted A. Skolarus, Rodney L. Dunn, Martin G. Sanda, Peter Chang, Thomas K. Greenfield, Mark S. Litwin, John T. Wei, Meredith Regan, Larry Hembroff, Dan Hamstra, Rodney Dunn, Laurel Northouse, David Wood, Eric A. Klein, Jay Ciezki, Jeff Michalski, Gerald Andriole, Mark Litwin, Chris Saigal, Thomas Greenfield, Louis Pisters, Deborah Kuban, Howard Sandler, Jim Hu, Adam Kibel, Douglas Dahl, Anthony Zietman, Andrew Wagner, and Irving Kaplan
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Gynecology ,Male ,medicine.medical_specialty ,business.industry ,Urology ,Urinary system ,MEDLINE ,Records ,Prostatic Neoplasms ,Urinary incontinence ,medicine.disease ,Article ,Clinical trial ,Prostate cancer ,Quality of life ,Internal medicine ,Surveys and Questionnaires ,Cohort ,medicine ,Quality of Life ,Humans ,Prospective Studies ,medicine.symptom ,Prospective cohort study ,business - Abstract
Objective To establish a score threshold that constitutes a clinically relevant change for each domain of the Expanded Prostate Cancer Index Composite (EPIC) Short Form (EPIC-26). Although its use in clinical practice and clinical trials has increased worldwide, the clinical interpretation of this 26-item disease-specific patient-reported quality of life questionnaire for men with localized prostate cancer would be facilitated by characterization of score thresholds for clinically relevant change (the minimally important differences [MIDs]). Methods We used distribution- and anchor-based approaches to establish the MID range for each EPIC-26 domain (urinary, sexual, bowel, and vitality/hormonal) based on a prospective multi-institutional cohort of 1201 men treated for prostate cancer between 2003 and 2006 and followed up for 3 years after treatment. For the anchor-based approach, we compared within-subject and between-subject score changes for each domain to an external "anchor" measure of overall cancer treatment satisfaction. Results We found the bowel and vitality/hormonal domains to have the lowest MID range (a 4-6 point change should be considered clinically relevant), whereas the sexual domain had the greatest MID values (10-12). Urinary incontinence appeared to have a greater MID range (6-9) than the urinary irritation/obstruction domain (5-7). Conclusion Using 2 independent approaches, we established the MIDs for each EPIC-26 domain. A definition of these MID values is essential for the researcher or clinician to understand when changes in symptom burden among prostate cancer survivors are clinically relevant.
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- 2015
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